Pain is the most common symptom for which patients seek medical advice and treatment. Pain can be acute or chronic. While acute pain is usually self-limited, chronic pain can persist for 3 months or longer and lead to significant changes in a patient's personality, lifestyle, functional ability or overall quality of life (K. M. Foley, Pain, in Cecil Textbook of Medicine 100–107, J. C. Bennett and F. Plum eds., 20th ed. 1996).
Pain has been traditionally managed by administering a non-opioid analgesic, such as acetylsalicylic acid, choline magnesium trisalicylate, acetaminophen, ibuprofen, fenoprofen, diflusinal and naproxen; or an opioid analgesic, such as morphine, hydromorphone, methadone, levorphanol, fentanyl, oxycodone and oxymorphone. Id.
U.S. Pat. No. 6,576,650 B1, U.S. Pat. No. 6,166,039, and U.S. Pat. No. 5,849,761, to Yaksh and U.S. Pat. No. 6,573,282, to Yaksh et al. describe 1,4 substituted piperidine derivatives allegedly useful as peripherally active anti hyperalgesic opiates.
U.S. Pat. No. 6,362,203 B1 to Mogi et al. describes 4 hydroxy-4-phenylpiperidine derivatives that are alleged to exhibit peripheral analgesic action.
Canadian Patent Publication No. 949560 of Carron et al. describes piperidine derivatives bearing substituents at the 1 and 4 positions that are alleged to be useful as analgesics.
International Publication No. WO 02/38185 A2 of Dunn et al. describes 1,4-substituted piperidine compounds that are allegedly useful as an antihyperalgesic opiate.
The Abstract of International Publication No. WO 01/70689 A1 also discloses piperidine derivatives carrying substituents at the 1 and 4 positions that are allegedly useful as opioid δ receptor agonists.
Traditional opioid analgesics exert their pharmacological activity once they have passed through the blood-brain barrier. But this blood-brain barrier passage can lead to undesirable central nervous system-mediated side effects, such as respiratory depression, increased drug tolerance, increased drug dependence, constipation and unwanted euphoria.
There remains a clear need for new drugs that are useful for treating or preventing pain or diarrhea and that reduce or avoid one or more side effects associated with traditional therapy for treating pain or diarrhea.
Citation of any reference in Section 2 of this application is not an admission that such reference is prior art to the present application.